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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina department of urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia Sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

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Neural Regeneration Research 2025年第8期20卷 2420-2432页

作者： Lin Yin Yalan Xu Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li Yin Wang Peifeng Li Hai Zhu Dong Wang Jing Li Institute for Translational Medicine The Affiliated Hospital of Qingdao UniversityMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina School of Basic Medicine Qingdao UniversityQingdaoShandong ProvinceChina College of Life Sciences and School of PharmacyMedical CollegeQingdao UniversityQingdaoShandong ProvinceChina department of urology Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdaoShandong ProvinceChina

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding *** of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully *** has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic ***,the function of CNKSR2 in the cytoplasm remains to be *** this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of *** a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the *** also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker *** colocalization analysis confirmed the centrosomal localization of *** we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal *** manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and ***,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum *** findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

关键词： autism spectrum disorder centrosome CNKSR2 intellectual disability interactome mass spectrometry microtubule neurodevelopmental disease protein complexes protein-protein interactions

Effects of extra-corporeal shock waves on penile hemodynamics and histopathology in rats

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Asian Journal of Andrology 2002年第4期4卷 249-253页

作者： Ahmet Tefekli Abdullah Armagan Bulent Erol Murat Celtik Isi Kilicaslan Asiye Nurten Ates Kadioglu department of urology Department of UrologyDepartment of UrologyDepartment of UrologyDepartment of Pathology Medical Faculty of IstanbulDepartment of Neuroscience Experimental Research Institution University of lstanbul TurkeyDepartment of Urology

Aim: To study the effect of extra-corporeal shock wave (ESW) on the penile hemodynamics and histopathology in rats. Methods: Adult male Sprague-Dawley rats were divided at random into 3 groups. ESW application was performed with a Siemens Lithostar with the rats under anesthesia lying prone on the balloon probe. Rats in Group Ⅰ received a total of 1000 shocks at 18 kV and immediately underwent hemodynamic evaluation performed by direct electrostimulation of the cavernous nerve and measurement of intracavernous pressure (ICP). Rats in Group Ⅱ received 3 times 1000 shocks at 18 kV at weekly intervals and hemodynamic evaluation was performed 1 month after the last ESW application. Group Ⅲ served as the control. Histopathological examinations of penile tissues were done on Masson's trichrome and hematoxylin and eosin stained sections. Results: Penile hemodynamic evaluation showed a trend toward a diminished mean maximal ICP, duration of erection, ICP during the plateau phase and maximal ICP/blood pressure ratio in Group Ⅰ, although there was no significant significance. The mean latency period in Groups Ⅰ and Ⅱ was prolonged. Petechial bleeding within tunical layers and small loci of hemorrhage within the corpora cavernosa were observed in Group Ⅰ. However, histopathological examination failed to reveal any significant differences between the groups in terms of smooth muscle content, tunical thickness, organization of collagen bundles and elastic fiber-lattice framework. Conclusion: ESW has certain damaging effects on the penis. (Asian J Androl 2002 Dec; 4: 249-253)

关键词： penis extra-corporeal shock wave Peyronie's disease tunica albuginea

Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic Surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of Medicine department of urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic Surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Lingual mucosal graft urethroplasty 12 years later: Systematic review and meta-analysis

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Asian Journal of urology 2019年第3期6卷 230-241页

作者： Alberto Abrate Andrea Gregori Alchiede Simonato department of Surgical Oncological and Oral SciencesSection of UrologyUniversity of PalermoPalermoItaly department of urology ASST RhodenseG.Salvini HospitalGarbagnate MilaneseMilanItaly

Objective:To evaluate the functional results and complications of the lingual mucosal graft(LMG)urethroplasty and to sum up the current state of the art of this surgical ***:A systematic search of PubMed and Scopus electronic databases was performed,according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)*** involving male patients treated with LMG urethroplasty for urethral stricture were *** protocol is available at http://***/PROSPERO/display_***?ID=CRD42017080121.A meta-analysis comparing functional and long-term oral complication outcomes of LMG and buccal mucosal graft(BMG)was performed,calculating the odds ratio(OR)and 95%confidence interval(CI).Results:Twenty original articles were included in the qualitative *** of 1.5e16.5 cm have been treated with LMG urethroplasty,due to the improvement of harvesting technique and very low rate of long-term oral *** good functional results have been reported by different authors for LMG urethroplasty,with lower rate of oral complications than *** meta-analysis included six comparative studies involving 187 and 178 patients treated with LMG and BMG urethroplasty,*** OR of 1.65(95%CI[0.95e2.87],I^2=0%)and 0.18(95%CI[0.03e1.26],I^2=68%)were found for LMG *** urethroplasty,in terms of success and oral complication rate,***:LMG urethroplasty can be reasonably considered a first choice technique for urethral stricture with very good *** complications are temporary and minimally disabling,basically less than those for BMG,and depend mainly on the graft extent.

关键词： Lingual mucosal graft Meta-analysis Systematic review Urethral stricture Urethroplasty

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype:Case study and literature review

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World Journal of Gastroenterology 2015年第11期21卷 3388-3393页

作者： Gustaw Lech Wojciech Korcz Emilia Kowalczyk Tomasz Guzel Marcin Radoch Ireneusz Wojciech Krasnodebski department of General Gastroenterological and Oncological SurgeryMedical University of Warsaw Students’ Scientific Group at department of General Gastroenterological and Oncological SurgeryMedical University of Warsaw

Gastrointestinal stromal tumours(GISTs) are the most common mesenchymal tumours of the gastrointestinal tract,but they represent less than 3% of all gastrointestinal tract *** is a detailed case study of a 52-yearold male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation,asymptomatic progress and late *** resected tumour,giant in diameters,was confirmed to represent the most rare histopathologic subtype of GISTs- sarcomatoid epithelioid *** report this case and review the literature with a special focus on pathomorphological evaluation,biological aggressiveness and prognostic *** our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid *** is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical *** tumours diagnosed at a late stage,which is often the case,can be large on *** for patients diagnosed with GIST depend on tumour size,mitotic rate,histopathologic subtype and tumour *** is why early diagnosis and R0 resection,which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs,are the key factors for further treatment and good prognosis.

关键词： Gastrointestinal stromal tumour Sarcomatoid epithe

TMED3 promotes prostate cancer via FOXO1a and FOXO3a phosphorylation

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Oncology research 2025年第1期33卷 161-169页

作者： Xiuwang Wei Jianbo Liang Huanwen Huang Daming Yang Xinxin Wang Xiujia Wang Changsheng Chen Kaiqiang Li Taisen Pang Bin Hu Fengning Wu department of urology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530000 China. department of Rehabilitation The People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530000 China.

Background:Transmembrane emp24 trafficking protein 3 (TMED3) is associated with the development of several tumors; however, whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:Short hairpin RNA was performed to repress TMED3 in prostate cancer cells (DU145 cells) and in a prostate cancer mice model to determine its function in prostate cancer and .Results:In the present study, we found that TMED3 was highly expressed in prostate cancer cells. , shTMED3 treatment suppressed the proliferation, invasion, and migration and promoted the apoptosis of DU145 cells. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor (FOXO) pathway. Furthermore, TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation. , TMED3 downregulation suppressed the apoptosis, growth, and metastasis of prostate cancer cells via FOXO1a and FOXO3a.Conclusion:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation, thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.

关键词： Apoptosis Proliferation Prostate cancer Transmembrane emp24 trafficking protein 3 (TMED3) forkhead box O transcription factor (FOXO)

Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital department of urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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